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Journal Reading :
RISK FACTORS FOR DEGENERATIVE SPONDYLOLISTHESIS:
A SYSTEMATIC REVIEW
Authors : John G DeVine 1, Jeannette M Schenk-Kisser 2, Andrea C Skelly 2
Institutions: 1Dwight D. Eisenhower Army Medical Center Fort Gordon, GA, USA
2Spectrum Research Inc, Tacoma, WA, USA
ABSTRACT
Study design: Systematic literature review.
Rationale: Many authors have postulated on various risk factors associated with the
pathogenesis of degenerative spondylolisthesis (DS), yet controversies regarding those risk
factors still exist.
Objective: To critically appraise and summarize evidence on risk factors for DS.
Methods: Articles published before October 15, 2011, were systematically reviewed using
PubMed and bibliographies of key articles. Each article was subject to quality rating and was
analyzed by two independent reviewers.
Results: From 382 citations, 30 underwent full-text review. Fourteen studies met inclusion
criteria. All but two were considered poor quality. Female gender and higher facet joint angle
were consistently associated with an increased risk of DS across multiple studies. Multiple
studies also consistently reported no association between back pain and prolonged
occupational sitting. Associations between age, parity, lumbosacral angle, lumbar lordosis,
facet joint tropism, and pelvic inclination angles were inconsistent.
Conclusions: There appears to be consistent evidence to suggest that the risk of DS increases
with increasing age and is greater for females and people with a greater facet joint angle.
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STUDY RATIONALE AND CONTEXT
Spondylolisthesis with an intact vertebral arch and associated advanced arthritic
changes in the facet joints at the level of vertebral displacement is termed
degenerativespondylisthesis (DS). The displacement most commonly occurs at the L4/L5
level and rarely exceeds 30% of the width of the adjacent vertebral body. Degenerative
spondylisthesis has been the subject of numerous studies since rst described by Junghanns
in 1930 [1]. Many authors have postulated on various risk factors associated with the
pathogenesis of DS, yet controversies regarding those risk factors and the etiology of DS still
exist.
OBJECTIVE
To critically appraise and summarize evidence on risk factors for DS.
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MATERIALS AND METHODS
Study design : Systematic review.
Search : PubMed and bibliographies of key articles (Fig 1) .
Dates searched : The search was conducted through October 15, 2011; no time limits
were placed on the search.
Inclusion criteria : Articles addressing the prognostic factors for lumbar degenerative
spondylolisthesis (Table 1) .
Exclusion criteria : Studies of patients with isthmic spondylolisthesis, fractures of the
lumbar spine, tumor, or iatrogenic spondylolisthesis were excluded.
Prognostic factors :
Sociodemographic/patient characteristics (age,gender, race, BMI,
pregnancy status/history)
Activity/work (occupational exposures, sport) Radiographic measures (disc height, lordosis/angles) Anatomical characteristics ( lumbar facet morphology)
Analysis : Descriptive.
RESULTS
From 382 citations, 30 underwent full-text review.Fourteen studies met the inclusion
criteria for assessingrisk factors associated with DS. All studies werecross-sectional;
most of which (12) were considered poor quality, only two were considered good
quality(CoE II), and only three considered confoundingfactors. Web Appendix
Section 4a provides the critical appraisal for these 14 studies, and Web Appendix
Section 6 describes the reasons for excluding studies.
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Common prognostic factors evaluated in multiple studies
Evidence across ve studies reporting on the association between age and risk of DS
is inconclusive, but studies that controlled for confounding suggest the risk of DS
increases with increasing age (Table 2).
Two studies used multivariate models to evaluate the association between age and
DS. In one, a 1-year increase in age was associated with a 9% increase in risk of DS
(odds ratio [OR] = 1.09; 95% condence interval [CI]: 1.01 1.17; P = .019) [2]. The
other reported a signicant association between age and DS only at levels L4 and L5
(OR not reported; P < .001 and P = .02, respectively) among women, and only at L4
(OR not reported; P < .001) among men [3].
In two studies which did not control for confounding, one reported a greater mean age
for patients with DS compared with controls (with DS: mean age, 68.2 years; range,
42 93 years; controls: mean age, 46.8 years; range, 21 69 years; statistical
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signicance not assessed)[4], and one reported no association between age and DS
[5].
Evidence across three studies suggests the risk of DS is higher for females.
One study which controlled for confounding reported a 2.4-fold (95% CI: 1.1 5.2; P= .01) and 4.0-fold (95% CI: 2.5 6.2; P < .001) increase in risk of DS at L3 and L4,
respectively for women. This study also reported a higher prevalence of DS among
women (women: 8.3%; men: 2.7%, P value not reported) [3].
Two additional studies, which did not control for confounding, also reported a
signicantly higher prevalence of DS among women (women: 37%; men: 10%; P .05).
Evidence across two studies evaluating the association between pelvic inclination
angle and DS was inconsistent.
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In one study [3], which controlled for confounding, women with DS had signicantly
greater pelvic inclination angle at L4 and L5 (means not reported by case status, and
ORs not reported; P = .009 and P = .007, respectively); however, there was no
association between pelvic inclination angle and DS among men.
In another study [13], which also controlled for confounding, patients with DS had a
signicantly lower sacral inclination angle (pelvic inclination angle) than controls
(36.42 10.05 versus 41.91 9.71, respectively; P < .01).
Prognostic factors evaluated in single studies (Table 4)
In single studies, the following characteristics were associated with DS: any and
bilateral oophorectomy, height and BMI (women only), heavy workload, practice of
sport and lifetime work exposure and prolonged occupational standing (both
associated with lower rate of DS) [2, 3, 12].
No association between the following characteristics and DS: unilateral
oophorectomy, weight, BMI and height (men), and job workload category, manual
material handling, load weight, professional vehicle driving, previous occupational
trauma, occupational psychosocial risk factors, age at menopause, standing, walking
and no daily repetitive lifting, and years lifting 50 250 20 kg/0 100 50 kg or 20
250 20 kg/10 100 50 kg daily [2, 3, 12].
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Radiographic measures evaluated in single studies (Table 5)
The following radiographic measures were associated with DS: traverse process
length, mean sagittal translation, and iliac crest height in single studies [4, 8, 13].
No association between the following radiographic measures and DS: traverse process
width and mean angular motion was reported in single studies [8, 13].
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DISCUSSION
The primary limitation of the evidence evaluating risk factors for DS is the poor
quality of studies. Twelve of 14 studies were CoE III, and only two were CoE II.
Most studies (all CoE III studies) did not attempt to control for confounding (Table
6).
In addition, comparison of results across studies is complicated due to the following
differences in the selected study populations:
The selection of DS cases differed substantially across studies, with some studies
restricting selection to patients with DS at L4 L5, and others including any DS
regardless of the level.
One study included patients who were undergoing surgery, which may be likely to
include more severe cases of DS [14].
Some studies selected only symptomatic DS subjects [2, 10, 12 15] and other studies
do not report whether DS subjects were symptomatic [4, 5, 7, 8, 11, 16].
One study selected older subjects [5], and some selected younger subjects [13], and in
two studies, there were substantial differences in age between DS cases and controls
[7, 16].
Most studies did not report whether cases were restricted to degenerative forms of
spondylolisthesis [2, 3, 5, 7, 8, 10 12, 14 16].
Some studies presented all analyses stratied by subpopulation (ie, oophorectomy
status, gender, level of DS) [3, 7, 8, 10 12].
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Our objective was to critically appraise and summarize evidence on risk factors for
DS. To this aim, we accomplished our goal. Typically, the aim of such an exhaustive
review is to identify risk factors that, from a clinical perspective, might be inuenced
by the clinician. For example, if the risk factor is environmental in nature and
modiable, steps could be formulated to decrease the risk, and ultimately inuence
the incidence or severity of the disease. If the risk factor is anatomical, it could be
amendable to closer observation, or even surgical correction to prevent the clinical
symptoms that accompany pathological progression.
In our systematic review, we found consistent evidence to suggest that the risk of DS
increases with increasing age and is greater for females and people with a greater
facet joint angle. Female gender and greater facet joint angle were consistently
associated with an increased risk of DS across multiple studies. Increased
sagittalization of the facet joints limits the ability to resist forward displacement, and
surgeons have recognized this anatomical variant and its association with
hypermobility and the development of DS (Figs 2 and 3). This anatomical variant,
although easily identiable, is not amendable to modication. Female gender has also
been long recognized as a risk factor and conrmed in our systematic review.
However, the explanation for this gender- specic risk has been largely inconclusive.
It is likely that changes in estrogen production and the resultant effect on soft tissues
play a role, but to what extent is unknown.
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The ideal method for studying the risk factors associated with the development of DS
includes a prospective analysis of a large group of patients from adolescence through
adulthood, making periodic assessment of all potential risk factors including
anatomical parameters via advanced imaging, hormonal levels, occupational
exposures, and in the future, possibly genetic analysis, accounting for confounding
variables. Although ideal, it would be costly, time consuming, and probably not
feasible particularly si nce it appears that the identi able risk factors are not
amendable to modication.
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